Colorectal cancer (CRC) is one of the most widespread tumor types, and it stands as the second leading cause of disease-related mortality globally. Due to its adverse effects, which lead to low patient adherence, new alternatives to conventional chemotherapy and radiotherapy treatments are being studied. Since, in most cases, platelets are positively involved in the persistence and progression of CRC, several elements of the platelet signaling pathway have been considered possible therapeutic targets. The present study assembles the main treatments for CRC and investigates the cellular mechanisms involved in the interaction between blood platelets and cancer cells. Additionally, this review cites other articles that propose possible therapeutic targets in the platelet activation pathways to be explored. Despite the reported benefits of antithrombotic therapy on CRC progression, some studies have warned about an increased bleeding risk and CRC incidence and highlight the importance of controlling this therapy through diagnostic tests. However, their high cost is still a significant obstacle to the population's access from low Human Development Index (HDI) countries. Many research groups have studied platelet signaling pathways in depth to develop a safer, more effective, and affordable therapy for the population.